PALB2: Options for Cancer Treatment

Cancer Treatment for People with Inherited PALB2 Mutations

Testing positive for an inherited PALB2 mutation may affect your treatment options or eligibility for clinical trials studying which treatments work best. The following are examples of situations where a PALB2 mutation may play a part in treatment decision-making. 

Breast cancer surgical decisions 

Because of the high risk for a second breast cancer diagnosis, women who are diagnosed with breast cancer who test positive for an inherited mutation in PALB2 may choose bilateral mastectomy rather than lumpectomy and radiation. Mutation carriers who undergo mastectomy are less likely to develop a second breast cancer. 

PARP inhibitors for cancer treatment

PARP inhibitors are a type of targeted therapy that work by blocking a protein used to repair damaged DNA. They were initially developed to treat cancers in people with an inherited BRCA1 or BRCA2 mutation. Since then, research and additional FDA approvals have expanded use of PARP inhibitors to more situations. People with a PALB2 mutation who have been diagnosed with cancer may want to ask their doctor about PARP inhibitor therapy. 
 

PARP inhibitors for early-stage and metastatic breast cancer

Although PARP inhibitors have not specifically received FDA approval to treat breast cancer in people with PALB2 mutations, the American Society of Medical Genetics released a paper suggesting that people with PALB2 mutations and cancer should be considered for the same treatments and clinical trials as people with a BRCA1 or BRCA2 mutation. Below are guidelines for PARP inhibitors for treating breast cancer in people with a BRCA1 or BRCA2 mutation. 

• Treatment for metastatic breast cancer: The PARP inhibitors, Lynparza (also known as olaparib) and Talzenna (also known as talazoparib) both have received FDA approval for treating metastatic breast cancer caused by a BRCA mutation.
• Treatment for early-stage breast cancer: Based on results from a large clinical trial, experts recommend one year of the PARP inhibitor olaparib for people with early-stage, HER2-negative breast cancer who have an inherited BRCA mutation and who are at high risk for recurrence.
   

PARP inhibitors for prostate cancer (mCRPC)

The PARP inhibitors, Lynparza (olaparib) and Talzenna (talazoparib) have received FDA approval to treat metastatic, castration-resistant prostate cancer in people with a PALB2 or other gene linked to a certain type of DNA damage repair. 

Clinical trials, such as NEPTUNE are looking at PARP inhibitors for treating early stage prostate cancer.

PARP inhibitors for advanced ovarian, fallopian tube or primary peritoneal cancer

Several PARP inhibitors have been approved to treat ovarian cancers at different stages of the disease. In some situations, a tumor biomarker test known as an HRD test ("homologous recombination deficiency") can help people with an inherited PALB2 mutation and advanced ovarian cancer learn if they may benefit from a PARP inhibitor. 

• Maintenance therapy after first-line treatment
  • HRD testing can help women with an inherited PALB2 mutation and advanced ovarian cancer learn if they may benefit from the PARP inhibitor Lynparza (olaparib) in combination with bevacizumab as maintenance therapy after first-line platinum chemotherapy.
  • Zejula is approved for maintenance therapy in women with advanced ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to first-line platinum-based chemotherapy. Zejula for maintenance therapy does not require an HRD test. 
• Maintenance therapy after treatment of recurrent cancer
  • Zejula and Rubraca (rucaparib) are both approved for maintenance therapy in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum based chemotherapy.

PARP inhibitors for pancreatic cancer

Although PARP inhibitors have not specifically received FDA approval to treat pancreatic cancer in people with PALB2 mutations, the American Society of Medical Genetics released a paper suggesting that people with PALB2 mutations and cancer should be considered for the same treatments and clinical trials as people with a BRCA1 or BRCA2 mutation. The PARP inhibitor Lynparza is FDA approved for maintenance treatment of pancreatic cancer in people with a BRCA mutation whose disease has not progressed after completing first-line platinum-based chemotherapy.

PARP inhibitors for other advanced cancers with no treatment options

If you have a PALB2 mutation and advanced cancer that no longer responds to standard therapy, you may want to talk with your doctor about whether you might benefit from treatment with a PARP inhibitor. 

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